Humoral and cellular immune responses in critically ill influenza A/H1N1‐infected patients

There is limited knowledge of influenza‐specific immune responses and their kinetics in critically ill patients. We investigated humoral and cellular immune responses after critical influenza A/H1N1 infection and hypothesized that dysfunctionality or absence of immune responses could contribute to more severe illness. We followed 12 patients hospitalized with severe influenza infection; the majority admitted to intensive care unit (ICU). Blood samples were collected at days 10 and 19 and at 5 months. Antibody responses to surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) of A/H1N1pdm09 were quantified by haemagglutination inhibition (HAI), microneutralization (MN), Enzyme‐linked immunosorbent assay (ELISA) and Enzyme‐linked lectin assay (ELLA). Influenza‐specific antibody levels and avidity were measured separately for head and stalk domains of H1. Cytokine secreting CD4+ and CD8+ T cell responses to conserved influenza epitopes (M1, NP and PB1) were analysed by FluoroSpot. Overall, the patients retained a high level of functional HA‐ and NA‐specific antibodies over the study period. During the acute phase (up to 3 weeks from symptom onset), antibodies specific to H1 stalk increased earlier and were present in higher amount compared with H1 head‐specific antibodies. The NA‐specific antibodies and the non‐neutralizing HA‐specific antibody response for H1 head and H1 full‐length showed a significant decline from acute to convalescent phase. Despite high total IgG concentrations, avidity to H1 head and H1 full‐length protein remained low at all time points. Similarly, CD8+ T cell responses were continuously measured at low levels. In conclusion, our study found that critically ill patients were characterized by low HA‐specific antibody avidity and CD8+ T cell response.